Evidence exists that HIV-seropositve smokers are at increased risk for developing pulmonary emphysema. Understanding the natural history of this phenomenon has important implications regarding lung disease in the setting of HIV. Furthermore, delineating important molecular mechanisms responsible for this accelerated process may have broad relevance regarding emphysema pathogenesis. In order to gain better insight into HIV- associated emphysema the current proposal seeks to address two specific aims: Specific Aim 1. To delineate the natural history of HIV-associated emphysema in the HAART era. In this aim we will test the hypothesis that parenchymal lung damage is attenuated in the HAART era. We will also examine the progression of physiologic abnormalities among a well characterized group with prominent gas exchange alterations. Specific Aim 2. In this aim we will compare the proteomes of alveolar macrophages obtained from HIV-seropositive smokers with and without emphysema. Successful completion of this project will enable us to further delineate the importance of smoking related lung damage occurring in the HIV-seropositive population. More importantly, the research proposed in this proposal will provide a unique opportunity to examine relevant mechanisms underlying the progression of early emphysema.